Over the years, several methods of administering biologically-active materials to mammals have been proposed. Many biologically-active materials, e.g., chemical compounds that can be described as medicinal agents, drugs, pharmaceuticals, etc., are available as water-soluble salts and can be included in pharmaceutical formulations relatively easily. Problems arise when the desired biologically-active material is either insoluble in aqueous fluids or is rapidly degraded in vivo. For example, alkaloids are often especially difficult to solubilize.
One way to solubilize biologically-active materials is to include them as part of a soluble prodrug. Prodrugs include chemical derivatives of a biologically-active chemical compound which, upon administration, eventually liberate the biologically-active material (hereinafter referred to e.g., as the drug or parent compound), in vivo. Linking the parent compound with a modifier moiety or moieties, to form a prodrug, allows the artisan to modify the onset and/or duration of action of the parent compound, in vivo. The artisan can also formulate prodrugs that can modify the transportation, distribution or solubility of a drug in the body. Furthermore, prodrug formulations often reduce the toxicity and/or otherwise overcome difficulties encountered when administering pharmaceutical preparations. Typical examples of prodrugs include those based upon organic phosphates, esters of alcohols, thioalcohols and other art-known derivatives. See Remington's Pharmaceutical Sciences, 16th Ed., A. Osol, Ed. (1980) (the disclosure of which is incorporated by reference).
Prodrugs are often biologically inert or substantially inactive forms of the parent compound. The rate of release of the active drug, i. e., the rate of hydrolysis of the prodrug, is influenced by several factors, but especially by the type of bond joining the parent drug to the modifier. Care must be taken to avoid preparing prodrugs which are eliminated through the kidney or reticular endothelial system, etc. before a sufficient amount of hydrolysis of the parent compound occurs. By incorporating a polymer as part of the prodrug system, one can increase the circulating half-life of the drug.
Thus, there continues to be a need for additional novel polymeric prodrug technologies. The present invention addresses this need.